Identification of an endogenous retroviral signature to predict anti-PD1 response in advanced clear cell renal cell carcinoma: an integrated analysis of three clinical trials.
ERV
ccRCC
nivolumab
predictive
prognostic
Journal
Therapeutic advances in medical oncology
ISSN: 1758-8340
Titre abrégé: Ther Adv Med Oncol
Pays: England
ID NLM: 101510808
Informations de publication
Date de publication:
2022
2022
Historique:
received:
11
03
2022
accepted:
26
08
2022
pubmed:
24
8
2023
medline:
24
8
2023
entrez:
24
8
2023
Statut:
epublish
Résumé
Endogenous retrovirus (ERV) elements are genomic footprints of ancestral retroviral infections within the human genome. Previous studies have demonstrated that dysregulated ERV transcription level is associated with immune cell infiltration in cancers, but the association between ERV expression and programmed cell death protein 1 (PD-1) blockade response is currently unraveled for solid cancers, such as advanced clear cell renal cell carcinoma (ccRCC). ERV mRNA profiles were obtained from three clinical trials of ccRCC where the patients were treated with anti-PD-1 (CM-009, CM-010, CM-025, and TCGA-KIRC data). Patients treated with nivolumab were divided into training and test cohort, while the TCGA-KIRC cohort was used as an external validation. Univariate Cox regression analysis and least absolute shrinkage and selection operator regression were used to establish the signature. Immune cell infiltration analysis and gene set enrichment analysis were performed to explore potential biological mechanisms. An ERV signature was established based on nine ERV expression patterns. In the training cohort, the median overall survival in the low- and high-risk group was 45.2 and 19.6 months [hazard ratio (HR) = 0.49, 0.32-0.75, The newly identified ERV signature is not only a prognostic, but also a predictive biomarker for advanced ccRCC patients who received anti-PD-1 therapy, which can guide personalized treatment in cancer patients in the future.
Sections du résumé
Background
UNASSIGNED
Endogenous retrovirus (ERV) elements are genomic footprints of ancestral retroviral infections within the human genome. Previous studies have demonstrated that dysregulated ERV transcription level is associated with immune cell infiltration in cancers, but the association between ERV expression and programmed cell death protein 1 (PD-1) blockade response is currently unraveled for solid cancers, such as advanced clear cell renal cell carcinoma (ccRCC).
Methods
UNASSIGNED
ERV mRNA profiles were obtained from three clinical trials of ccRCC where the patients were treated with anti-PD-1 (CM-009, CM-010, CM-025, and TCGA-KIRC data). Patients treated with nivolumab were divided into training and test cohort, while the TCGA-KIRC cohort was used as an external validation. Univariate Cox regression analysis and least absolute shrinkage and selection operator regression were used to establish the signature. Immune cell infiltration analysis and gene set enrichment analysis were performed to explore potential biological mechanisms.
Results
UNASSIGNED
An ERV signature was established based on nine ERV expression patterns. In the training cohort, the median overall survival in the low- and high-risk group was 45.2 and 19.6 months [hazard ratio (HR) = 0.49, 0.32-0.75,
Conclusion
UNASSIGNED
The newly identified ERV signature is not only a prognostic, but also a predictive biomarker for advanced ccRCC patients who received anti-PD-1 therapy, which can guide personalized treatment in cancer patients in the future.
Identifiants
pubmed: 37614979
doi: 10.1177/17588359221126154
pii: 10.1177_17588359221126154
pmc: PMC10442641
doi:
Types de publication
Journal Article
Langues
eng
Pagination
17588359221126154Informations de copyright
© The Author(s), 2022.
Déclaration de conflit d'intérêts
The authors declare no relevant conflict of interest regarding this manuscript. M.H. reports collaborations with Merck Serono (advisory role, speakers’ bureau, honoraria, travel expenses, research funding); MSD (advisory role, speakers’ bureau, honoraria, travel expenses, research funding); AstraZeneca (research funding); Novartis (research funding); BMS (advisory role, honoraria, speakers’ bureau); Teva (travel expenses). U.S.G. and P.R.F. received support for presentation activities for Dr Sennewald Medizintechnik GmbH, have received support for investigator initiated clinical studies (IITs) from MSD and AstraZeneca and contributed at Advisory Boards Meetings of AstraZeneca and Bristol-Myers Squibb.